Loading...
Please wait, while we are loading the content...
Similar Documents
Integrin β1-mediated acquired gefitinib resistance in non-small cell lung cancer cells occurs via the phosphoinositide 3-kinase-dependent pathway.
| Content Provider | Europe PMC |
|---|---|
| Author | DENG, QIN-FANG SU, BO ZHAO, YIN-MIN TANG, LIANG ZHANG, JIE ZHOU, CAI-CUN |
| Copyright Year | 2015 |
| Abstract | The present study aimed to explore the role of integrin β1 and the relevant signaling pathways in acquired gefitinib resistance in non-small cell lung cancer (NSCLC). The inhibitory effects of gefitinib, with or without LY294002, on cellular proliferation were evaluated by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were analyzed by flow cytometry, while western blotting was used to evaluate the expression of EGFR, phosphorylated (phospho)-EGFR, protein kinase B (Akt), phospho-Akt, extracellular signal-regulated kinase (Erk) and phospho-Erk. The gene expression profiles of PC9 and PC9/G cells were determined by DNA microarray. Integrin β1 was knocked down in PC9/G cells by transiently transfected short interfering RNA (siRNA). A scrambled siRNA sequence was used as a control. Apoptosis of transfected cells was determined by Annexin V-phycoerythrin-Cy5/propidium iodide staining. Sequencing products were amplified by nested PCR. The resistant index of PC9/G cells to gefitinib was ~138- to 256-fold higher than that of PC9 cells, and this resistance was accompanied by significant increase in integrin β1 expression in PC9/G cells. Knockdown of integrin β1 with short hairpin RNA in PC9/G cells markedly inhibited proliferation and enhanced apoptosis in response to gefitinib, restoring the sensitivity of PC9/G cells gefitinib. Phosphoinositide 3-kinase (PI3K)/Akt activation was observed in PC9/G cells in the presence of gefitinib and the sensitivity of PC9/G cells to gefitinib was also able to be restored by PI3K/Akt pathway inhibitor LY294002. Finally, knockdown of integrin β1 significantly reduced the levels of phospho-Akt. These findings suggest that integrin β1 signaling via the PI3K/Akt pathway may be a significant mechanism underlying gefitinib resistance, and may potentially present an alternative therapeutic target for the treatment of NSCLC unresponsive to EGFR inhibitors. |
| ISSN | 17921074 |
| Journal | Oncology Letters |
| Volume Number | 11 |
| PubMed Central reference number | PMC4727211 |
| Issue Number | 1 |
| PubMed reference number | 26870244 |
| e-ISSN | 17921082 |
| DOI | 10.3892/ol.2015.3945 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2015-11-18 |
| Access Restriction | Open |
| Rights License | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Deng et al. |
| Subject Keyword | drug resistance epidermal growth factor receptor inhibition tyrosine kinase inhibitor integrin |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
